One of the most exciting developments in memory research over the past five years is the discovery of a link between the ability to remember the past and the ability to envision the future. The bulk of the supporting evidence for this link comes from neuroimaging studies in normal cognition, which demonstrate that thinking about the future engages a core set of brain structures that have traditionally been associated with episodic remembering. These findings have inspired new ways of thinking about the function of episodic memory, re- casting its purpose as one of facilitating the generation or simulation of alternative future scenarios in the service of planning and decision-making. A limitation of neuroimaging studies, however, is that they cannot address the necessity of activated brain areas for task performance; such information must come from studies of patients with lesions to candidate brain areas. Thus, an important source of evidence about the functional link between memory and future thinking comes from amnesic individuals, who have lesions to medial- temporal lobe structures and consequent impairments in episodic memory. To date, such research has been limited to a handful of studies predominated by examination of individual cases. The present proposal represents a systematic investigation of the relationship between memory and future thinking in amnesia, using both behavioral and neuroimaging techniques. The first part of the proposal comprises a series of behavioral experiments aimed at: elucidating the nature and extent of the future thinking impairment in amnesia; testing alternative theories about the cognitive mechanisms that characterize hippocampal contributions to future thinking; and exploring ways to ameliorate the future thinking impairment in amnesia. The second part of the proposal represents the first examination in amnesia of the default network, a constellation of brain areas that have been implicated in future thinking in normal cognition. These neuroimaging studies will allow us to examine whether impairments in future thinking in amnesia are associated with reduced connectivity and/or activation in regions of the default network that have previously been linked to future thinking. Further, these studies will elucidate the effect of a focal lesion in one part of the default network (the medial temporal lobe) on the correlated activity among other structures within the default network. The studies comprising this proposal have the potential to deepen our understanding of the cognitive and neural underpinnings of future thought, to provide important constraints on theories of future thinking and its relation to episodic memory, and to shape interventional approaches to a variety of clinical disorders in which future thinking is implicated. PUBLIC HEALTH RELEVANCE: Recent research has revealed a link between the ability to remember the past and the ability to envision the future. In this study, we will investigate the relationship between memory and future thinking in amnesic individuals, who have marked deficits in remembering the past. Our findings may shape interventional approaches to a variety of clinical disorders in which memory and future thinking may be implicated.